Apparatus, system, and method of archival and retrieval of samples

ABSTRACT

A sample archive method and system implement a plurality of sample carriers configured to support a plurality of sample nodes in a predetermined spatial relationship, sample storage devices for selectively placing the plurality of sample carriers in an archive, and sample node removal apparatus for locating and removing selected ones of the plurality of sample nodes. Alternative embodiments are disclosed wherein the sample node removal apparatus comprises a laser and a mechanical clipping tool, which may be manually operated or automated. An optical component may be operative to detect the location of selected sample carriers in the archive, selected ones of the plurality of sample nodes, or both. A positioning component may position the sample node removal apparatus responsive to signals transmitted by the optical component. Various apparatus and methods of archiving samples and preparing the same for analysis are also disclosed.

The present application is related to non-provisional application Ser.No. 10/007,355, filed Nov. 7, 2001, entitled “SAMPLE CARRIER” and alsoto non-provisional application Ser. No. 10/005,415, filed Nov. 7, 2001,entitled “ARCHIVE AND ANALYSIS SYSTEM AND METHOD” the disclosures ofwhich are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

Aspects of the present invention relate generally to archival of samplematerial, and more particularly to a system and method of archiving andretrieving biological or non-biological samples maintained in desiccatedform at a plurality of sample nodes on a carrier.

DESCRIPTION OF THE RELATED ART

In many applications such as pharmaceutical and medical research, lawenforcement, and military identification, for example, it is oftendesirable to have access to numerous biological samples. Conventionalbiorepositories or other sample storage facilities utilize liquid or lowtemperature cryogenic systems for sample storage; these liquid andcryogenic systems are expensive both to create and to maintain.Additionally, current technology generally presents system operatorswith complicated and labor intensive maintenance and administrativeresponsibilities.

Specifically, the intricacies of cryogenic systems may typically obligetechnicians, researchers, and system operators to engage in coordinatedlabor for weeks to retrieve and to prepare thousands of deoxyribonucleicacid (DNA) samples from whole blood. Accordingly, conventionalapproaches for archiving DNA in liquid or cryogenic states arefundamentally inadequate to the extent that they do not accommodate highvolume processing and sample throughput. Current research trendsrecognize benefits associated with systems and methods of archiving andretrieving biological and non-biological samples which may be capable ofprocessing thousands of samples per day; current technology, however, isinadequate to attain throughput at this level. In fact, current systemsand methods cannot attain processing throughput of one hundred or moresamples per day.

Although some small volume liquid-state DNA and blood archivaltechniques have been useful in the past, present methodologies are notcapable of supporting the increasing storage and retrieval ratesrequired as advancing genomics technology becomes more prevalent as aresearch and diagnostic tool. Since the traditional cryogenic-basedarchival format is difficult and expensive to automate, systems basedupon existing technology are generally not amenable to the highthroughput demands of the market.

Recently, biological research laboratory systems have been proposedwhich incorporate archiving and retrieval of blood samples in dry ordesiccated form. Present systems are generally based upon modificationsor variations of known techniques for storing DNA or other organicsamples on a suitable substrate such as filter paper; some systemsrequire, or substantially benefit from, soaking the substrate or paperwith chemical denaturants and detergents prior to use. In any event,however, existing desiccated sample archival systems are manuallyoperated or only partially automated, and hence do not meet the highvolume processing demands of the market. Additionally, these systemsemploy a mechanical punch or other tool which is operative to removesamples from substrates, typically by punching through or otherwisephysically engaging the substrate material. Consequently, these toolsnecessarily make contact with multiple samples during ordinary use.

In that regard, those of skill in the art will appreciate that even ifthe current substrate-based archive systems were fully automated,significant cross contamination problems would undoubtedly remain.During the sample removal punching process, extraneous fibers adhere tothe punching tool or are otherwise released from the substrate,contaminating subsequent samples handled by the tool. Thesecontamination problems limit both the utility and the practicality oftraditional technologies. Moreover, the density of the storage facilityis ultimately limited by the inherent saturation limit of the substrate,as well as by the precision of mechanical and robotic components of thesystem.

In particular, full automation of the storage and retrieval processes insystems employing conventional filter paper or substrate card formatswould necessarily require very precise robotics and other machineryoperating repeatedly to identify, to retrieve, and to replace individualstorage cards within a large volume storage room or vault. Althoughprecise, high-resolution robotic systems are currently available, finelytuned precision is achieved only when the mechanisms are operated withina small area. Accordingly, automating the storage and retrieval processfor filter paper card or other substrate-based archival systems withinan entire large scale vault is not a practical solution given currentmechanical and robotic limitations.

SUMMARY

Embodiments of the present invention overcome various shortcomings ofconventional technology, providing a system and method of automatedarchival and retrieval of desiccated biological or non-biologicalsamples. In accordance with one aspect of the invention, for example, afully automated desiccated sample storage system may be operative toachieve very high storage and retrieval rates, for example, greater thanone hundred samples per day. An archive management system may include orsupport some or all of the following, inter alia: patient consenting;questionnaire transcription; blood deposition; sample bar coding;archive storage; electronic sample browsing; sample retrieval; samplepurification and extraction; and sample packaging and shipping. Coupledwith the internet or other wide-area or local network, a fully automatedarchive facility may accommodate efficient search and timely transportof biological or other samples, as well as attendant data and otherinformation, throughout the world.

As set forth in detail below, the foregoing system and method may employa desiccated sample carrier configured and operative to facilitateefficient and timely access to contamination-free samples. In accordancewith this aspect of the present invention, a sample carrier mayaccommodate very high sample densities at room temperature.Consequently, archive density may be satisfactory for high throughputdemands, while the expense and complications associated with cryogenicor liquid sample storage facilities may be reduced or eliminated.

In accordance with one aspect of the present invention, for example, asample carrier comprises a structural array and a plurality of samplenodes; each of the plurality of sample nodes being removably attached tothe structural array at a respective attachment point and operative tocarry a discrete sample. In some embodiments, each of the plurality ofsample nodes is operative to carry a biological sample, includingproteins, polynucleotides, and DNA; in some alternative embodiments,each of the plurality of sample nodes is operative to carry anon-biological sample.

In accordance with another aspect of the present invention, the samplecarrier further comprises identifying indicia, some of which aredecipherable by an optical sensor. In some embodiments, each of theplurality of sample nodes comprises an associated transceiver operativeto transmit a unique signal; additionally, the associated transceivermay be operative to receive a control signal from a remote device.

Depending upon, inter alia, the type of sample and overall systemrequirements of the various embodiments, each of the plurality of samplenodes is solid or porous. Sample carrier embodiments are disclosedwherein each of the plurality of sample nodes comprises a sample supportmedium, which may comprise cellulose, a polymer such as polystyrene, orother material. In accordance with some embodiments, the sample supportmedium is derivatized, and may be positively charged or negativelycharged.

In another embodiment a sample carrier comprises a plurality ofstructural arrays supported in a predetermined spatial relationship anda plurality of sample nodes, wherein each of the plurality of samplenodes is removably attached to one of the plurality of structural arraysat a respective attachment point and operative to carry a discretesample. An alternative is disclosed wherein each of the plurality ofstructural arrays is supported in a predetermined spatial relationshiprelative to a respective sample container, such as a respective well ofa multi-well plate.

In the foregoing embodiment employing a plurality of structural arrays,all of the alternatives and features mentioned above with reference tothe single structural array embodiment are incorporated.

In accordance with another aspect of the present invention, a method oftransferring a specimen to a sample carrier comprises providing a samplecarrier comprising a structural array supporting a plurality of samplenodes, and contacting the plurality of sample nodes to the specimen.Various alternatives are disclosed wherein the specimen is solid,gaseous, and liquid in form.

In some embodiments, the method further comprises selectively applying apreservative to the plurality of sample nodes subsequent to thecontacting; it may be desirable that the preservative is operative todesiccate the specimen transferred to the plurality of sample nodes.

The method may further comprise washing the plurality of sample nodessubsequent to the contacting. Additionally or alternatively, as notedabove, the method may further comprise allowing the plurality of samplenodes to desiccate subsequent to the contacting, with or without theassistance of a preservative.

In accordance with another aspect of the present invention, a method oftransferring specimens to a sample carrier comprises providing a samplecarrier comprising a plurality of structural arrays, each of theplurality of structural arrays being supported in a predeterminedspatial relationship relative to a respective specimen container andsupporting a plurality of sample nodes, and contacting the plurality ofsample nodes supported by selected ones of the plurality of structuralarrays to a respective specimen. In some embodiments, the contactingcomprises bringing the plurality of sample nodes supported by each ofthe plurality of structural arrays into contact with a specimen in therespective specimen container.

In the foregoing embodiment employing a plurality of structural arrays,all of the alternatives and features mentioned above with reference tothe single structural array embodiment are incorporated.

In some embodiments, a sample carrier comprises: a structural arraycomprising a plurality of sample nodes, wherein each of the plurality ofsample nodes is removably attached to the structural array at arespective attachment point and comprises a discrete sample supportmedium; and a specimen carried by the sample support medium at one ormore of the plurality of sample nodes.

In some embodiments, the specimen is biological, including proteins,polynucleotides, and DNA; in some alternative embodiments, the specimenis non-biological.

Depending upon, inter alia, the type of sample and overall systemrequirements of the various embodiments, the sample support medium issolid or porous. Sample carrier embodiments are disclosed wherein thesample support medium comprises cellulose, a polymer such aspolystyrene, or other material. In accordance with some embodiments, thesample support medium is derivatized or treated with a chemicalcompound, and may be positively charged or negatively charged.

In accordance with another aspect of the invention, a sample archivesystem comprises a plurality of sample carriers configured to support aplurality of sample nodes in a predetermined spatial relationship,sample storage means for selectively placing the plurality of samplecarriers in an archive, and sample node removal means for locating andremoving selected ones of the plurality of sample nodes. Alternativeembodiments are disclosed wherein the sample node removal meanscomprises a laser and a mechanical clipping tool.

In some embodiments, the system comprises an optical component operativeto detect the location of the selected ones of the plurality of samplenodes; it may be desirable that such a system further comprises apositioning component operative to position the sample node removalmeans responsive to signals transmitted by the optical component.

In some embodiments, a sample archive system comprises a plurality ofsample carrier receptacles, each of the plurality of sample carrierreceptacles configured to receive one or more sample carriers supportinga plurality of sample nodes, a sample carrier storage device operativeto place selected ones of the one or more sample carriers in selectedones of the plurality of sample carrier receptacles, a sample carrierlocation device operative to locate the selected ones of the one or moresample carriers, a sample carrier retrieval device operative to retrievethe selected ones of the one or more sample carriers from ones of theplurality of sample carrier receptacles, and sample node removal meansfor identifying and removing selected ones of the plurality of samplenodes.

In some embodiments, at least a portion of the plurality of samplecarrier receptacles includes a rack, while in other embodiments, atleast a portion of the plurality of sample carrier receptacles includesa drawer. Embodiments of the system are disclosed wherein the samplecarrier location device is a bar code reader. Additionally oralternatively, embodiments of the system are disclosed wherein thesample node removal means comprises a laser and a mechanical clippingtool.

A system is disclosed wherein the sample node removal means furthercomprises an optical component operative to detect the location of theselected ones of the plurality of sample nodes; in some embodiments, thesample node removal means may further comprise a positioning componentoperative to position a laser responsive to signals transmitted by theoptical component.

In some embodiments, it may be desirable that the system furthercomprise means for processing a sample supported by the selected ones ofthe plurality of sample nodes, or a controller for controlling operationof the sample carrier storage device and the sample carrier retrievaldevice.

In accordance with a further aspect of the present invention, a samplearchive system comprises an archive comprising a plurality of samplecarrier receptacles, each of the plurality of sample carrier receptaclesconfigured to receive one or more sample carriers supporting a pluralityof sample nodes, and a robotics system comprising mechanisms operativeto store and to retrieve selected ones of the one or more samplecarriers from the archive. The foregoing system may comprise a samplecarrier locator coupled to the robotics system and operative to detect alocation of the selected ones of the one or more sample carriers.

In some embodiments of the system, the sample carrier locator comprisesan optical sensor; a system is further disclosed wherein the roboticssystem is automatically responsive to signals from the sample carrierlocator. As noted above, a system may further comprise a sample noderemoval device operative to identify and to remove selected ones of theplurality of sample nodes from selected ones of the one or more samplecarriers. A sample node locator coupled to the sample node removaldevice may be operative to detect a location of the selected ones of theplurality of sample nodes. Embodiments are disclosed wherein the samplenode removal device is automatically responsive to signals from thesample node locator, which may comprise an optical sensor or arespective transceiver incorporated in each of the plurality of samplenodes. The system may include a sample carrier locator embodied in a barcode reader.

In some systems, the sample node removal device comprises a mechanicalclipping tool and a mechanical positioning system to position themechanical clipping tool relative to the selected ones of the pluralityof sample nodes, whereas in other systems, the sample node removaldevice comprises a laser and a mechanical positioning system to positionthe laser relative to the selected ones of the plurality of samplenodes. Embodiments are disclosed wherein the mechanical positioningsystem is operative to position the clipping tool or the laserresponsive to signals transmitted by an optical sensor. As noted above,such systems may further comprise means for processing a samplesupported by the selected ones of the plurality of sample nodes. In somealternative embodiments, the system further comprises a computeroperative to control the robotics system and the sample node removaldevice.

In accordance with still another aspect of the present invention, amethod of archiving samples comprises selectively transferring aspecimen to a plurality of discrete sample nodes attached to a samplecarrier, archiving the sample carrier in an archive facility, andrecording the location of the sample carrier in the archive facility.Embodiments of the foregoing method further comprise washing theplurality of discrete sample nodes subsequent to the selectivelytransferring, while other embodiments additionally or alternativelycomprise assigning identifying indicia, such as a bar code, for thesample carrier in accordance with the recording. The recording maycomprise writing data records associated with the plurality of discretesample nodes to a computer readable data storage medium.

Another method of archiving samples comprises obtaining a specimen froma source, associating an identifier to the source and to the specimen,writing the identifier and information associated with the source andthe specimen to a data structure, selectively transferring the specimento a plurality of discrete sample nodes attached to a sample carrier andplacing the sample carrier in a sample carrier receptacle at an archivefacility. The foregoing method may further comprise recording thelocation of the sample carrier in the archive facility; additionally oralternatively, the method may further comprise acquiring consent toobtain the specimen.

In some embodiments, the method comprises assigning identifying indicia,such as a bar code, for the sample carrier in accordance with theassociating and the selectively transferring. As noted above, therecording may comprise writing data records associated with theplurality of discrete sample nodes to a computer readable data storagemedium.

A computer readable medium is disclosed which is encoded with data andcomputer executable instructions; the data and instructions causing anapparatus executing the instructions to: receive information regarding asample and a source of the sample; assign an identifier to the sample,the source, and the information; record the identifier and theinformation in a data structure; and record the location within a samplecarrier of each of a plurality of discrete sample nodes supporting thesample.

The computer readable medium may further cause an apparatus to transmitcontrol signals to a remote device at an archive facility. Additionallyor alternatively, some embodiments of the computer readable mediumfurther cause an apparatus to transmit control signals to a sample noderemoval device operative to locate and to remove selected ones of theplurality of discrete sample nodes, or to transmit control signals to asample carrier storage device operative to place selected ones of aplurality of sample carriers in an archive. In the latter embodiment,the computer readable medium may additionally cause an apparatus totransmit control signals to a sample carrier retrieval device operativeto retrieve the selected ones of the plurality of sample carriers fromthe archive.

In accordance with one aspect of the present invention, a method ofpreparing an archive sample for analysis comprises identifying a sampleto be analyzed, responsive to the identifying, ascertaining a locationof the sample on a discrete sample node supported by a sample carrier,responsive to the ascertaining, removing the discrete sample node fromthe sample carrier, and preparing the sample for analysis.

Embodiments of the foregoing method are disclosed wherein theidentifying comprises interrogating a data structure such as a database.In some embodiments, the ascertaining comprises utilizing an opticalsensor, which may include reading a bar code. Alternatively, theascertaining comprises identifying a unique signal transmitted from atransceiver attached to the discrete sample node; in this embodiment,the removing may comprise transmitting a control signal to thetransceiver.

As in the embodiments described above, methods are disclosed wherein theremoving comprises utilizing a laser or a mechanical clipping tool. Thepreparing may comprise depositing the discrete sample node in a samplecontainer; additionally or alternatively, the preparing may comprisewashing sample material attached to the discrete sample node.

In the foregoing method, the composition of the sample (i.e.non-biological, biological, etc.) is as described above; accordingly,the method may further comprise amplifying a polynucleotide.

In some embodiments, a method of preparing an archive sample foranalysis comprises receiving a request related to an experiment,identifying a sample suitable for the experiment, responsive to thereceiving and the identifying, locating a sample carrier supporting thesample on a discrete sample node, detecting a location of the discretesample node on the sample carrier, removing the discrete sample nodefrom the sample carrier, and preparing the sample for analysis. As notedabove, the locating may comprise any or all of the following:interrogating a database maintaining records related to the samplecarrier; utilizing an optical sensor; and reading a bar code.

In accordance with one aspect of the method, the detecting comprisesobtaining video signals output from an optical sensor; accordingly, theremoving may comprise automatically or manually operating a sample noderemoval device responsive to the obtaining video signals. Additionallyor alternatively, the detecting comprises identifying a unique signaltransmitted from a transceiver attached to the discrete sample node; inthis embodiment, the removing may comprise transmitting a control signalto said transceiver.

In another embodiment, a sample node removal system comprises a samplecarrier configured to support a plurality of sample nodes in apredetermined spatial relationship, and node removal means for locatingand removing selected ones of said plurality of sample nodes. The noderemoval means may be embodied in the hardware, such as a laser or amechanical clipping tool, and computerized elements described above. Anoptical component may be operative to detect the location of theselected ones of the plurality of sample nodes; in some embodiments,signals output from the optical component may be used in conjunctionwith a positioning component operative to position the node removalmeans responsive to signals transmitted by said optical component. Asnoted above, such a system may further comprise a computer operative toreceive the signals and to control the positioning component and thenode removal means.

In another embodiment, a method of preparing an archive sample foranalysis comprises identifying a sample to be analyzed, responsive tothe identifying, obtaining the sample, preparing the sample foranalysis, and selectively repeating the identifying, the obtaining, andthe preparing at a rate sufficient to prepare in excess of 100 samplesfor analysis per day. As noted above, the identifying may compriseinterrogating a database, utilizing an optical sensor, or both. Theobtaining may comprise automatically or manually operating a sample noderemoval device, which may be a laser or a mechanical clipping tool.

Aspects of the methods previously discussed may be incorporated into theforegoing embodiment. Additionally, the selectively repeating may occurat a rate sufficient to prepare in excess of 200 samples for analysisper day; methods are disclosed wherein the selectively repeating occursat a rate sufficient to prepare in excess of 500 samples for analysisper day.

In some embodiments, a method of providing biological analyses to aremote client comprises maintaining a sample archive comprising aplurality of discrete sample nodes, receiving a request for a biologicalanalysis from a remote client, the request comprising identification ofa selected sample node from the plurality of discrete sample nodes andidentification of a selected assay, responsive to the receiving,retrieving the selected sample node from the archive and preparing theselected assay, and performing the selected assay for the selectedsample node.

The method of providing biological analyses may further comprisetransmitting results of the performing and data representative of theperforming to the remote client; the transmitting may include encryptingthe results and the data. In some embodiments, the method mayadditionally comprise shipping the selected sample node to the remoteclient. The request may be received via a network connection.

Embodiments of the foregoing method are disclosed wherein the assay is agenomics experiment or a proteomics experiment, for example, and whereinthe retrieving the selected sample node comprises some or all of thefollowing: interrogating a database; utilizing an optical sensor; andautomatically or manually operating a sample node removal device, whichmay comprise a laser or a mechanical clipping tool. As with the methodspreviously described, a method of providing biological analyses mayfurther comprise washing the sample prior to the performing.

In accordance with another aspect of the invention, a method ofproviding samples to a remote client comprises maintaining a samplearchive comprising a plurality of discrete sample nodes, receiving arequest, via a network connection or otherwise, for a sample from aremote client, responsive to the receiving, identifying a selected oneof the plurality of discrete sample nodes in the archive, the selectedone of the plurality of discrete sample nodes carrying the sample,retrieving the selected one of the plurality of sample nodes from thearchive, and shipping the selected one of the plurality of sample nodesto the remote client.

In some embodiments, the method may further comprise performing ananalysis of the sample prior to the shipping, and may additionallycomprise transmitting results of the performing and data representativeof the performing to the remote client. The above-mentioned shipping maycomprise packaging the selected one of the plurality of sample nodes ina sample container. As noted above, methods are disclosed furthercomprising washing the selected one of the plurality of sample nodesprior to said shipping.

The above-mentioned identifying may comprise interrogating a database,while the above-mentioned retrieving may comprise utilizing an opticalsensor, automatically or manually operating a sample node removaldevice, or both. The sample node removal device comprises a laser or amechanical clipping tool, depending upon the embodiment and overallsystem requirements, for example.

In some embodiments including performing an analysis of the sample, theanalysis is a genomics experiment, whereas in other embodiments, theanalysis is a proteomics experiment.

In accordance with yet another aspect of the present invention, a systemcomprises a sample archive comprising a plurality of sample carriers,each of the plurality of sample carriers configured to support aplurality of discrete sample nodes, a database containing data recordsassociated with ones of the plurality of discrete sample nodes and datarecords associated with biological analyses, means for receiving arequest from a remote client, the request containing information relatedto performing a selected analysis with selected ones of the plurality ofdiscrete sample nodes, a processor responsive to the means for receivingand operative to retrieve selected ones of the data records from thedatabase, a sample retrieval apparatus responsive to the processor andoperative to retrieve the selected ones of the plurality of discretesample nodes, an assay preparation apparatus responsive to the processorand operative to prepare an assay in accordance with the selectedanalysis, and means for conducting the selected analysis with theselected ones of the plurality of discrete sample nodes and forproviding results of the selected analysis to the processor.

Such a system may further comprise means for packaging the selected onesof the plurality of discrete sample nodes for shipping to the remoteclient. Embodiments of the system are disclosed wherein the sampleretrieval apparatus comprises a sample carrier locator operative todetect a location of selected ones of the one or more sample carriers.As noted above, the sample carrier locator may comprise an opticalsensor or a bar code reader. Embodiments of the system include a sampleretrieval apparatus comprising a sample node removal device operative toremove the selected ones of the plurality of discrete sample nodes fromthe plurality of sample carriers.

The sample retrieval apparatus may further comprise an optical sensor;as described above with reference to other aspects of the invention,embodiments of the foregoing system are disclosed wherein the samplenode removal device is responsive to signals transmitted from theoptical sensor. The sample node removal device comprises a laser in someembodiments, and a mechanical clipping tool in others.

In some systems, the sample node removal device comprises a laser and amechanical positioning system operative to position the laser relativeto the selected ones of the plurality of discrete sample nodesresponsive to the signals transmitted from an optical sensor;alternatively, the sample node removal device comprises a mechanicalclipping tool and a mechanical positioning system operative to positionthe mechanical clipping tool relative to the selected ones of theplurality of discrete sample nodes responsive to the signals transmittedfrom an optical sensor. As noted above, the sample node removal devicemay comprise a respective transceiver incorporated in each of theplurality of discrete sample nodes. In some embodiments, the analysisperformed by the system is a genomics experiment, and in otherembodiments, the analysis is a proteomics experiment.

A computer readable medium encoded with data and computer executableinstructions is disclosed; the data and instructions causing anapparatus executing the instructions to receive a request from a remoteclient for performing a selected analysis of a selected sample nodemaintained on a sample carrier in a sample archive, retrieve datarecords associated with the selected sample node and the selectedanalysis from a database, retrieve the selected sample node from thesample carrier, prepare an assay in accordance with the selectedanalysis, and conduct the selected analysis of a specimen carried on theselected sample node.

The computer readable medium may further cause an apparatus to provideresults of the selected analysis and data related to the selectedanalysis to the remote client. The computer readable medium may furthercause an apparatus to transmit control signals to a sample carrierretrieval device operative to retrieve the sample carrier from a samplecarrier receptacle at an archive facility. Additionally, this computerreadable medium may further cause an apparatus to transmit controlsignals to a sample carrier storage device operative to place the samplecarrier in the sample carrier receptacle. As set forth above withreference to computer readable media aspects, in some embodiments, acomputer readable medium may further cause an apparatus to transmitcontrol signals to a sample node removal device operative to locate andto remove the selected sample node from the sample carrier.

In accordance with still another aspect of the present invention, asystem comprises a sample archive, a database containing data recordsassociated with samples stored in the archive, means for receiving arequest from a remote client, the request containing information relatedto selected ones of the samples, a processor responsive to the means forreceiving and operative to retrieve selected ones of the data recordsfrom the database, a sample retrieval apparatus responsive to theprocessor and operative to retrieve the selected ones of the samples, asample preparation apparatus responsive to the processor and operativeto prepare the selected ones of the samples for analysis, and means forpackaging the selected ones of the samples for shipping to the remoteclient, wherein the sample retrieval apparatus, the sample preparationapparatus, and the means for packaging are operative at a ratesufficient to retrieve, to prepare, and to package in excess of 100samples per day.

The foregoing system may further comprise means for conducting aselected analysis, such as a genomics experiment or a proteomicsexperiment, for example, with the selected ones of the samples and forproviding results of the selected analysis to the processor.

As noted above, in some embodiments of the system, the sample retrievalapparatus comprises some or all of the following: an optical sensor, alaser, a mechanical clipping tool, or a transceiver.

In some embodiments, the sample retrieval apparatus, the samplepreparation apparatus, and the means for packaging are operative at arate sufficient to retrieve, to prepare, and to package in excess of 200samples per day; in still other embodiments, the rate may be sufficientto retrieve, to prepare, and to package in excess of 500 samples perday.

The foregoing and other aspects of various embodiments of the presentinvention will be apparent through examination of the following detaileddescription thereof in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified block diagram illustrating one embodiment of anautomated sample archival and retrieval system.

FIG. 2 is a simplified block diagram illustrating the general operationof one embodiment of an automated sample archival and retrieval system.

FIG. 3 is a simplified block diagram illustrating components of oneembodiment of a sample archive facility and automated archive managementsystem.

FIG. 4A is a simplified diagram illustrating one embodiment of a samplecarrier.

FIG. 4B is a simplified partial longitudinal cross section of a samplecarrier constructed to engage a multi-well plate.

FIG. 4C is a simplified partial transverse cross section of a samplecarrier constructed to engage a multi-well plate.

FIG. 5A is a simplified diagrammatic plan view illustrating oneembodiment of a structural array employed by a sample carrier.

FIG. 5B is a simplified illustration of various embodiments of a samplenode.

FIG. 5C is a simplified block diagram illustrating one embodiment of asystem and method of removing a sample node from a sample carrierstructural array.

FIG. 5D is a simplified block diagram illustrating another embodiment ofa system and method of removing a sample node from a sample carrierstructural array.

FIG. 5E is a simplified block diagram illustrating one embodiment of asample node identification or location system.

FIG: 6 is a simplified flow diagram illustrating one embodiment of amethod of preparing an archive sample for analysis.

FIG. 7 is a simplified flow diagram illustrating one embodiment of asample archival method.

FIG. 8 is a simplified flow diagram illustrating one embodiment of amethod of retrieving and preparing an archive sample for analysis.

DETAILED DESCRIPTION

Turning now to the drawings, FIG. 1 is a simplified block diagramillustrating one embodiment of an automated sample archival andretrieval system. In the exemplary FIG. 1 embodiment, system 100generally comprises one or more remote computers or terminals, such asnetwork client 110, coupled to one or more servers, such as server 130,via a communications network 199. System 100 may also comprise datastorage media and peripheral equipment, represented by referencenumerals 141 and 120, respectively.

For clarity, only one server 130 and one client 110 have been depictedin FIG. 1. Those of skill in the art will appreciate that thearrangement illustrated in FIG. 1 is presented for illustrative purposesonly, and that system 100 may be implemented with any number ofadditional servers, clients, or other components; the number and varietyof each device coupled to network 199 may vary in accordance with systemrequirements. In some embodiments, the functionality of one device, suchas peripheral device 120, for example, may reside on or be enabled byanother device, such as server 130.

In operation, client 110 may be capable of two-way data communicationvia communications network 199. In that regard, client 110 maycommunicate with server 130, peripheral device 120, and data storagemedium 141 via network 199 or via one or more additional networks (notshown) which may be coupled to network 199. It will be appreciated bythose of skill in the art that client 110, server 130, and othercomponents depicted in FIG. 1 may be coupled via any number ofadditional networks without inventive faculty.

In some embodiments, client 110 may be a personal computer orworkstation, a personal digital assistant (PDA), a wireless telephone,or other network-enabled computing device, electronic apparatus, orcomputerized system. In operation, client 110 may execute software orother programming instructions encoded on a computer-readable storagemedium, and additionally may communicate with server 130, data storagemedium 141, and peripheral device 120 for monitor and controlapplications. For example, client 110 may interrogate server 130 andrequest transmission of data maintained at data storage medium 142coupled to, or accessible by, server 130. Additionally or alternatively,client 110 may transmit control signals or requests which may causedevice 120 to take some action or to execute a specified function orprogram routine.

It is well understood in the art that any number or variety ofperipheral equipment, such as device 120, may additionally be coupled tonetwork 199 without departing from the essence of the presentdisclosure. Examples of such peripheral devices include, but are notlimited to: servers; computers; workstations; terminals; input/outputdevices; laboratory equipment; printers; plotters; routers; bridges;cameras or video monitors; sensors; actuators; or any othernetwork-enabled device known in the art. Peripheral device 120 may becoupled to network 199 directly, as illustrated in FIG. 1, orindirectly, for example, through server 130, such that the functionalityor operation of device 120 may be influenced or controlled as describedbelow by hardware or software resident on server 130.

As is generally known in the art, server 130 may be embodied orimplemented in a single physical machine, for example, or in a pluralityof distributed but cooperating physical machines. In operation, server130 may incorporate all of the functionality of a file server orapplication server, and may additionally be coupled to data storagemedium 142 and sample archive facility 160.

In that regard, information and data records maintained at data storagemedium 142 and sample archive facility 160 may be accessible to client110 through bidirectional data communication with server 130 via network199.

Network 199 may be any communications network known in the artincluding, for example: the internet; a local area network (LAN); a widearea network (WAN); a Virtual Private Network (VPN); or any systemproviding data communication capability between client 110, server 130,storage medium 141, and peripheral device 120. In addition, network 199may be configured in accordance with any topology known in the art,including star, ring, bus, or any combination thereof.

By way of example, the data connection between components in FIG. 1 maybe implemented as a serial or parallel link. Alternatively, the dataconnection may be any type generally known in the art for communicatingor transmitting data across a computer network; examples of suchnetworking connections and protocols include, but are not limited to:Transmission Control Protocol/Internet Protocol (TCP/IP); Ethernet;Fiber Distributed Data Interface (FDDI); ARCNET; token bus or token ringnetworks; Universal Serial Bus (USB) connections; and Institute ofElectrical and Electronics Engineers (IEEE) Standard 1394 (typicallyreferred to as “FireWire”) connections.

Other types of data network interfaces and protocols are within thescope and contemplation of the present disclosure. In particular, client110 may be configured to transmit data to, and receive data from, othernetworked components using wireless data communication techniques, suchas infrared (IR) or radio frequency (RF) signals, for example, or otherforms of wireless communication. Accordingly, those of skill in the artwill appreciate that network 199 may be implemented as an RF PersonalArea Network (PAN).

Storage media 141,142 may be conventional read/write memory such as amagnetic disk drive, a magneto-optical drive, an optical disk drive, afloppy disk drive, a compact-disk read only memory (CD-ROM) drive, adigital versatile disk read only memory (DVD-ROM), a digital versatiledisk random access memory (DVD-RAM), transistor-based memory, or othercomputer-readable memory device for storing and retrieving data.

Sample archive facility 160 may be arranged and configured to maintain amultiplicity of biological or non-biological samples in desiccated formas set forth in more detail below. Additionally or alternatively,archive facility 160 may include mechanical and robotic systemsconfigured and operative to manipulate samples and to facilitatewashing, purification, testing, packaging, and shipping thereof. Varioustesting devices, experimental apparatus, and research equipment may haveaccess to the samples maintained at archive facility 160. Computerhardware and software resident at, or operatively coupled to mechanicaland other components at, archive facility 160 may communicate withserver 130 as illustrated in FIG. 1. In the exemplary FIG. 1 embodiment,archive facility 160 represents the foregoing samples, equipment,robotics, devices, and computer hardware and software, as well as anetwork interface enabling bi-directional data communication betweencomputer components in archive facility 160 and server 130.

FIG. 2 is a simplified block diagram illustrating the general operationof one embodiment of an automated sample archival and retrieval system.As illustrated in FIG. 2, client 210 may generally correspond to client110 depicted and described above with reference to FIG. 1. Similarly,server 230, storage medium 242, and sample archive facility 260 maycorrespond to server 130, storage medium 142, and archive facility 160,respectively. The components in the FIG. 2 arrangement may incorporateall of the respective functionality set forth above.

Responsive to requests or instructions from client 210, for example,server 230 may be operative to retrieve data or information from storagemedium 242 and archive facility 260. Storage medium 242 may comprise adatabase, for instance, or other data structure configured to maintaindata records and other information related to some or all of thefollowing: the number and type of samples maintained in archive facility260; sample origins or sources; testing or research procedures orprotocols; operational parameters of various components incorporated inarchive facility 260; and access authorization, passwords, billinginformation, and the like associated with client 210. The foregoing listis provided by way of example only, and is not intended to be inclusive.

As illustrated in FIG. 2, storage medium 242 and archive facility 260may be configured to engage in two-way data communication such thatcomputer hardware or systems at archive facility 260 may read datarecords from, and write data to, storage medium 242. Alternatively, asillustrated and described below with reference to FIG. 3, various datastorage media may be incorporated in archive facility 260, for example.

FIG. 3 is a simplified block diagram illustrating components of oneembodiment of a sample archive facility and automated archive managementsystem. The exemplary FIG. 3 sample archive facility 360 may generallycorrespond to archive facilities 160 and 260 described above withreference to FIGS. 1 and 2, respectively, and may incorporate all of thefunctionality and operational characteristics set forth above. Archivefacility 360 may generally comprise a system coordination component(coordinator) 310, a mechanical systems control component (controller)320, and an archive and laboratory component (archive) 330.

System coordinator 310 may include computer hardware and softwareconfigured to manipulate or to instruct other system elements as setforth in detail below. Accordingly, coordinator 310 may be embodied in acomputer server or other electronic control system, for example, and maybe configured to run a multi-tasking operating system (OS 316) as isgenerally known in the art. Coordinator 310 generally comprises at leastone processor 311 coupled to other components described below via asystem bus (not shown). Processor 311 may be any microprocessor ormicrocontroller-based microcomputer known in the art.

The software code or programming instructions for controlling thefunctionality of processor 311 may be encoded in memory 312 or stored instorage medium 315. Memory 312 and storage medium 315 may be anycomputer-readable memory known in the art, as discussed above.Additionally or alternatively, some software or instruction code relatedto operation of processor 311 may reside at a remote device or storagemedium 242 as described above with reference to FIG. 2. Networkinterface hardware and software, such as represented by communicationinterface 319A and network software 317, respectively, may facilitatethe foregoing network communication, and may generally enable anyinterface known in the art for communicating or transferring filesacross a computer network as set forth in detail above.

Processor 311 may communicate via the system bus with a plurality ofperipheral equipment, including network interface 319A, for example,enabling two-way network data communications as described above.Additional peripheral equipment may be incorporated in or coupled tocoordinator 310; in some embodiments, such peripheral equipment mayinclude an input device 313 and an output device 314 enabling a systemadministrator, researcher, or other technician to interface withcoordinator 310 for monitor and control purposes. Examples of peripheralinput/output devices may include the following: conventional keyboards,keypads, trackballs, or other input devices; visual displays such ascathode ray tube (CRT) monitors, liquid crystal display (LCD) screens,touch-sensitive screens, or other monitor devices known in the art fordisplaying graphical images and text; microphones or other audio oracoustic sensor devices; audio speakers; and the like. It will beappreciated by those of skill in the art that peripheral equipment mayinclude suitable digital-to-analog and analog-to-digital conversioncircuitry (not shown), as appropriate.

In operation, coordinator 310, under control of processor 311 and OS316, for example, may execute instruction code or application software318 configured and operative to provide desired functionality forarchive facility 360 as a whole. In some embodiments, for instance,archive facility 360 may be configured to locate and to retrieveselected biological or non-biological samples and to prepare the samefor shipping to a remote site for experimentation or further storage.Additionally or alternatively, various components of archive facility360 may be employed to perform selected experiments with, or related to,retrieved samples. Overall functionality of archive facility 360 may beselectively altered or controlled in accordance with data and computerexecutable instructions, OS 316, and application software 318 undercontrol of processor 311. In an alternative embodiment, much of theautomated functionality of archive facility 360 described below may bemanual, or provided by a researcher or technician, for example.

Coordinator 310 may communicate with controller 320 via data signalstransmitted through communication interface 319B. In that regard,controller 320 may incorporate a communication interface 329 operativeto enable bi-directional data communication with coordinator 310. In oneembodiment, the data interface between coordinator 310 and controller320 may be implemented in the form of a wire-line (i.e. “hard-wired”),as represented by the double-headed arrow in FIG. 3. By way of example,the data connection may be a serial, parallel, or Ethernet link, or anyother type of communication coupling, such as described above, generallyknown in the art for communicating or transmitting data across acomputer network.

Other types of data interfaces and protocols are contemplated asdescribed above. In particular, as represented by the “lightning bolt”symbol in FIG. 3, coordinator 310 may be configured to transmit data to,and receive data from, controller 320 using wireless IR or RF signals,for example, or other forms of wireless communication. In a wirelessembodiment, coordinator 310 and controller 320 may be capable ofcommunicating via the Bluetooth(TM) standard, for example.

Controller 320 may additionally include a processor 321, memory 322, anda mechanical interface 323; though not illustrated in the FIG. 3embodiment, controller 320 may additionally incorporate or be coupled toa data storage medium, which may store data and configurationinstructions related to overall operation of controller 320.

Software code, configuration information, or programming instructionsrelated to or influencing the functionality of processor 321 may beencoded in memory 322, for example; additionally or alternatively,processor 321 may receive data and instructions from coordinator 310 viacommunication interface 329, or from an additional data source asdescribed above.

In operation, controller 320 may transmit control signals or other dataand instructions to affect operation of a device, apparatus, machine,robotic equipment, or other mechanism via mechanical interface 323. Thebidirectional data communication interface between controller 320 andthe apparatus to be controlled may generally correspond to the datainterfaces and protocols described above. As indicated in FIG. 3,controller 320 and the machinery to be monitored or controlled may becoupled via wire-line or wireless communication connections.

It will be appreciated that controller 320 may include one or moreadditional mechanical interfaces 323, depending upon a variety offactors such as the number of mechanisms to be controlled, the overallcapabilities of processor 321, the capacity of memory 322, the datatransmission bandwidth of mechanical interface 323, and the desiredfunctionality of the archive facility 360, for example. Additionally oralternatively, archive facility 360 may comprise one or more additionalcontrollers operative to manipulate or to control additional mechanisms;in one embodiment, for example, each machine or device maintained atarchive facility 360 may be controlled by a respective dedicated controlcomponent such as controller 320.

In the FIG. 3 embodiment, robotic equipment or other mechanisms(robotics 331) to be monitored or controlled by controller 320 arerepresented as maintained or housed within archive 330. In addition torobotics 331 and associated computer hardware and software required foroperation thereof, archive 330 may generally comprise a biological ornon-biological sample archive (sample storage 332), instrumentation andequipment 333, and data storage medium 334.

As depicted in the high-level FIG. 3 block diagram, equipment 333generally represents a wide array of experimental apparatus andinstrumentation, laboratory supplies and functional paraphernalia, andthe like; the type, construction, and overall configuration of equipment333 maintained at archive 330 may be a function of the intendedoperational characteristics of archive facility 360, the state andorganization of the samples maintained in sample storage 332, and otherfactors. Examples of equipment 333 may include test tubes, microtiter orother multi-well plates, laboratory pipettes, storage vessels, shippingboxes and other packaging materials, scales or balances, and so forth.Those of skill in the art will appreciate that the scope of the presentdisclosure is not limited by the nature or characterization of equipment333, and that different types of apparatus may be required in accordancewith the desired functionality of archive facility 360.

In some embodiments, for example, archive facility 360 may serve as alarge scale repository and source for biological or non-biologicalsamples; accordingly, equipment 333 in such an embodiment may includeappropriate containers or receptacles for accommodating samples duringshipping, packing material and shipping boxes or envelopes, scales orbalances for weighing samples or shipping materials, and so forth.Additionally or alternatively, archive facility 360 may be constructedand operative to serve as a central laboratory or experimental servicesprovider. In this latter embodiment, robotics 331 may includeproprietary or standardized laboratory modules dedicated to performingspecific experiments with biological and non-biological samples, forinstance, and equipment 333 may include pipettes and other liquidcontainers, microtiter plates constructed to receive multiple samples,antigens, reagents and other chemicals, and so forth.

Robotics 331 in the FIG. 3 embodiment of archive facility 360 mayrepresent a wide range of equipment and devices such as, for example:control modules implemented in computer hardware or software;computer-based or electronically controlled machinery, servos, hydraulicsystems, and the like; electronic circuits; peripheral equipment such asautoclaves, thermocyclers, or centrifuges; and any other devices to becontrolled by controller 320 via mechanical interface 323. In somebiological or non-biological sample archives, for example, robotics 331may be embodied in machine vision apparatus, optical sensors orscanners, bar code readers, and the like, which may identify particularsamples from among the plurality of samples in sample storage 332; thisidentification may be automatic, for example, or under control of anoperator or administrator through input/output devices 313,314 atcoordinator 310.

Various robotic or automated devices are known in the art for retrievingand transporting samples or sample carriers. Accordingly, robotics 331may comprise automatically controlled arms or gripping devices which maybe translated or otherwise manipulated in three dimensions. Suchrobotics 331 may generally be configured and operative to retrieveselected samples or sample carriers from sample storage 332 and tomanipulate retrieved sample carriers in accordance with data andinstructions received from processor 321 at controller 320. Those ofskill in the art will appreciate that robotics 331 may comprise computerhardware and software (not shown) sufficient to enable the bidirectionaldata communication illustrated in FIG. 3; additionally, some embodimentsof robotics 331 may include powerful processors, for example, coupled tomachine vision or other sample carrier identification devices such asbar code readers or optical sensors as described above.

In addition to placing, identifying, retrieving, and manipulatingsamples or sample carriers stored or archived at sample storage 332,robotics 331 may further be operative to utilize equipment 333 requiredfor conducting desired operations on or with respect to samples. Asnoted above, these operations may include washing, purification,alteration, testing or experimental analysis, replacing, packaging,shipping, and the like.

In that regard, robotics 331 may be embodied in, for example: samplestorage devices or means operative to place samples or sample carriersinto receptacles at sample storage 332; sample location devices, whichmay employ optical sensors or machine vision technology as describedabove, for locating particular samples or sample carriers from among theplurality archived at sample storage 332; sample retrieval devices ormeans for retrieving selected sample carriers from sample storage 332;and sample node removal devices, which also may employ optical sensorsas described below. Alternatively, a technician employed at archivefacility 360 may place sample carriers into sample carrier receptacles,identify, locate and retrieve sample carriers, and manipulate samplesmanually.

Data storage medium 334 may be embodied in the types of hardwaredescribed above, and may maintain data records related to the samplesdeposited in sample storage 332, operational parameters of robotics 331and other mechanized or automated devices, and the availability andvariety of equipment 333. For example, storage medium 334 may maintaindata records associated with each sample in sample storage 332,including, but not limited to: the nature or type of sample (e.g. blood,DNA, protein, environmental particles or pollutants); the source ororigin of the sample; the date the sample was archived; the number oftimes the sample has been retrieved; the tests or experiments conducted;and the like. Similarly, storage medium 334 may include data recordsrelated to the available supply of multi-well plates or other samplevessels at archive 330, the maintenance schedule for various roboticequipment, and so forth. It will be appreciated that data records andother information maintained at storage medium 334 may be transmitted tostorage medium 315 at coordinator 310; such transmission may occurperiodically, for example, at predetermined time intervals, orresponsive to specific requests or interrogations from processor 311.

The nature and variety of robotics 331 and equipment 333 employed atarchive 330 may generally be influenced by the manner and form in whichsamples are maintained and stored in sample storage 332. For example,where samples are stored in conjunction with an identifying bar codelabel, robotics 331 may comprise a bar code reader. Since, as notedbriefly above, certain automated or other robotic systems are known forretrieving, handling, and replacing different types of laboratorycontainers and sample carriers, sample storage 332 may be constructedand configured for use with existing machines as set forth in moredetail below.

Sample storage 332 may generally comprise a plurality of sample carrierreceptacles, each of which may be configured to receive one or moresample carriers. Sample carrier receptacles may be implemented asdrawers, shelves, or racks, for example. In some embodiments, samplestorage 332 may be an environmentally controlled vault or otherstructure designed to maintain samples at a constant or optimum humidityand temperature; environmental parameters may be selected in accordancewith the type and state of the samples. Alternatively, the entirearchive 330 may be contained within a single environmentally controlledvault.

FIG. 4A is a simplified diagram illustrating one embodiment of a samplecarrier. In the FIG. 4A embodiment, sample carrier 410 generallycomprises a frame structure having a longitudinal axis represented bythe dashed line 499. Carrier 410 may include one or more transverse(relative to longitudinal axis 499) members such as designated byreference numeral 412 and a plurality of sample site positioning members413, each of which may accommodate one or more sample site members414,415 in a predetermined spatial relationship. Though only threetransverse members 412 are illustrated in FIG. 4A, sample carrier 410may be scaled to include any number of additional transverse members 412as desired; alternatively, fewer than three transverse members 412 maybe appropriate in certain situations.

A structural array, such as designated by reference numerals 420A–420C,configured and operative to maintain a plurality of samples as set forthin more detail below, may be supported at each sample site member414,415. It is noted that the depiction of structural arrays 420A–420Cis representative only, and that certain physical components ofstructural arrays 420A–420C have been omitted from FIG. 4A for clarity;the particular characterization is not intended to be interpreted in anylimiting sense.

As in the illustrated embodiment, sample carrier 410 may be constructedsuch that each structural array 420A–420C is supported in apredetermined spatial relationship relative to other structural arraysand relative to a respective specimen or sample container. By way ofexample, structural array 420A may be supported in a position to engagea respective well 431A in a multi-well plate 430, while structural array420B may be supported to engage a different respective well 431B inmulti-well plate 430.

In the exemplary embodiment depicted in FIG. 4A, each structural arrayin a given row of sample sites on sample carrier 410, e.g. row 416, maybe supported in a predetermined spatial relationship relative to arespective specimen or sample container in a corresponding row of wellsin multi-well plate 430, i.e. row 436 in this example. Similarly eachstructural array in row 417 (e.g. structural array 420C) may besupported to engage a respective well in row 437 of multi-well plate430.

Sample carrier 410 may additionally include longitudinal frame elements418A,418B which may support transverse members 412. In some embodiments,longitudinal elements 418A,418B may be constructed and operative tosupport a label, tag, decal, or other identifying indicia 419 which maybe unique to sample carrier 410. As is generally known in the art,identifying indicia 419 may incorporate a bar code, a serial number, orother alpha-numeric or symbolic representation, for example, and maydistinguish sample carrier 410 from other sample carriers maintained inan archive facility such as illustrated and described above withreference to FIG. 3.

Structural elements of sample carrier 410 may be constructed of anymaterial with sufficient rigidity to support structural arrays 420A–420Cin a desired predetermined spatial relationship, which may beinfluenced, for example, by the configuration or arrangement ofrespective sample containers such as an array of test tubes or the wellsof a multi-well plate. Additionally, longitudinal elements 418A,418B maybe constructed and dimensioned to enable manipulation and transport ofsample carrier 410 by robotics or other automated mechanisms;consequently, longitudinal elements 418A,418B may be constructed ofappropriate material to withstand forces exerted by handling or grippingmechanisms. Accordingly, the structural elements of sample carrier 410may be fabricated of polystyrene or various plastics, for example, andmay provide suitable stiffness without rendering sample carrier 410unnecessarily heavy or cumbersome.

FIG. 4B is a simplified partial longitudinal cross section, and FIG. 4Cis a simplified partial transverse cross section, of a sample carrierconstructed to engage a multi-well plate. The cross sectional viewdepicted in FIG. 4B is taken along longitudinal axis 499 in FIG. 4A,whereas the cross sectional view depicted in FIG. 4C is taken along therow 416/436 in FIG. 4A. As indicated in FIGS. 4B and 4C, transversemember 412 may support sample site positioning members 413 such thateach sample site member 414,415 (and consequently, its associatedstructural array 420A–420C) is accurately positioned relative to arespective specimen or sample container (wells 431A–431C) in amulti-well plate 430. As with the illustration in FIG. 4A, structuralarrays 420A–420C are depicted in representative form for clarity.

In some embodiments, multi-well plate 430 may include one or moretransverse depressions 432; referring back to FIG. 4A, it will beappreciated that depression 432 may be oriented orthogonal tolongitudinal axis 499 and disposed intermediate rows 436,437 of wells431. Depression 432 may be dimensioned to allow acceptance of transversemember 412 when sample carrier 410 is brought sufficiently close tomulti-well plate 430. Similarly, multi-well plate 430 may include one ormore longitudinal depressions 433 (FIG. 4B) dimensioned to receivesample site positioning members 413 when sample carrier 410 is broughtsufficiently close to multi-well plate 430.

Specimen containers such as wells 431A–431C may contain specimenmaterial to be transferred to structural arrays 420A–420C. Afterappropriate alignment, which may be facilitated by automated mechanismsor robotics, for example, or conducted manually, sample carrier 410 andmulti-well plate 430 may be brought into close proximity such thattransverse member 412 enters depression 432, sample site positioningmember 413 enters depression 433, and structural arrays 420A–420Ccontact respective specimens contained in wells 431A–431C. In theforegoing manner, specimen material may be transferred to discretesample nodes (described below with reference to FIGS. 5A–5E) atstructural arrays 420A–420C.

Wells such as 431A–431C in various multi-well plates known in the artmay be particularly suited to accommodate specimen material in liquidform; it will be appreciated, however, that wells 431A–431C may alsocarry specimen material in solid or even gaseous form. As noted above,specimens may be biological or non-biological, for example. Biologicalspecimen material may include biopolymers such as proteins or otherpolynucleotides, e.g. DNA. Examples of non-biological specimens mayinclude chlorofluorocarbons or other environmental or atmosphericpollutants.

Following transfer of sample material to structural arrays 420A–420C,sample carrier 410 may be engaged with a clean, or previously unused,multi-well plate 430 for sample storage and preservation. In thisembodiment, sample containers such as wells 431A–431C of multi-wellplate 430 may not contain any specimens or other material, and mayprotect samples maintained at structural arrays 420A–420C fromcontamination introduced by external sources or by contact with otheritems. Since depression 432 is configured to accommodate transversemember 412 and depression 433 is configured to accommodate sample sitepositioning member 413, the combination of sample carrier 410 andmulti-well plate 430 may accept a cover (not shown) as is generallyknown in the art of preserving samples in multi-well plates.

Longitudinal elements 418A,418B may extend beyond the longitudinal sides432A,432B of multi-well plate 430 and the sides of any cover or lid. Agripping or handling apparatus oriented for use along longitudinal axis499 may engage longitudinal elements 418A,418B and remove sample carrier410 (and any lid disposed thereon) from multi-well plate 430; on theother hand, a gripping or handling apparatus oriented for use along thetransverse axis may engage transverse sides 433A,433B of multi-wellplate 430, and consequently, the entire assembly of multi-well plate430, sample carrier 410, and cover. In the foregoing embodiment, astandard plate cover may be modified to allow protrusion of transversemembers 412 and longitudinal elements 418A,418B.

FIG. 5A is a simplified diagrammatic plan view illustrating oneembodiment of a structural array employed by a sample carrier.Structural array 520A generally corresponds to those represented anddescribed above with reference to FIGS. 4A–4C. The arrangement andoverall configuration of structural array 520A is provided by way ofexample only. In some embodiments, structural array 520A may befabricated of the same material, such as polystyrene or other polymer,for example, as the sample carrier to which it is attached.

Structural array 520A generally comprises a plurality of samplestructures such as designated by reference numerals 522 and 524. Samplestructures 522,524 may be maintained in a predetermined spatialrelationship by radial elements 521 or other suitable structuralcomponents. In the exemplary embodiment, a sample node (represented bythe small circles in FIG. 5A, one of which is designated by referencenumeral 529) may be removably attached to structural array 520A at arespective one of the sample structures 522,524; i.e. each samplestructure 522,524 may be operative to support a discrete sample node529. In turn, each sample node 529 may be operative to carry a discretesample, such as biological or non-biological sample material, forexample. Such samples may include, for example, proteins orpolynucleotides.

Sample nodes 529 may be removably attached to sample structures 522,524at attachment points 523,525, respectively. In some embodiments,attachment points 523,525 may be free from specimen material or othercontaminants such that selective removal of sample nodes 529, even bymechanical means requiring physical contact with attachment points523,525, does not introduce cross contamination risks generated byforeign material, residue from previous removal operations, or otherparticulate matter.

It will be appreciated that sample nodes 529 need not be circular, norof uniform size, as represented in FIG. 5A, but may be formed in any ofnumerous other shapes and sizes. FIG. 5B is a simplified illustration ofvarious embodiments of a sample node. Those of skill in the art willappreciate that several polygons, polyhedrons, and spherical or oblongshapes are contemplated and may be selected based upon various factorssuch as the desired node size and density, the saturation limit of thematerial used for nodes 529, the accuracy and precision of the deviceused to remove nodes 529 as described below, and the like. The presentdisclosure is not intended to be limited by the shape, size, ordimensional characteristics of sample nodes 529.

A sample node 529 such as illustrated and described may generallycomprise, or be constructed entirely of, a sample support medium; insome embodiments, for example, sample node 529 may simply be coated witha selected sample support medium. In accordance with one aspect of thepresent invention, sample support media for use at sample nodes 529 maybe embodied in paper or cellulose, polystyrene, plastic, or othersuitable support material constructed and operative to serve as along-term storage mechanism for biological or other samples in adesiccated form. Specimen material in solid, liquid, or gaseous form maybe brought into contact with the sample support medium and stored assamples at discrete sample nodes 529.

In some embodiments, for example, such a sample support medium maymaintain desiccated samples of biopolymers, including DNA and proteins,or non-biological samples, including fluorocarbons orchlorofluorocarbons (CFCs) and synthetic chemical compounds. As notedabove, filter paper substrate embodiments are currently known in theart; the present disclosure is not to be construed as so limited,however. A support medium suitable for implementation at sample nodes529 may generally comprise any appropriate material known in the art ordeveloped and operative in accordance with known principles, and may beselected in accordance with binding properties as a function of the typeof sample to be carried and maintained.

In that regard, an appropriate sample support medium may be solid orporous, for example, depending, in part, upon the type of specimen to bestored as samples at discrete sample nodes 529. Additionally oralternatively, sample support medium may be treated with one or morechemical compounds or derivatized, for instance, to manipulate variousbinding properties prior to contact with a specimen. Positive ornegative electrical charges, chemical compositions, bindingcharacteristics, antibodies, lectins, porosity, and other operationalfactors for sample nodes 529 may be selected in accordance with the typeof sample support medium implemented and the type or nature of anyprocesses performed thereon.

Biological and non-biological samples may be stored in a controlledenvironment. In that regard, humidity, temperature, and otherenvironmental factors may be controlled in a fireproof vault or otherstructure employed as an archive as set forth above. In someembodiments, environmental conditions may be selectively altereddepending, for instance, upon the nature of the samples, the compositionof the sample support medium employed at sample nodes 529, or both, topreserve longevity of the samples for decades. In a DNA archivalembodiment, for example, the sample support medium may include achemically treated surface or structure, serving to lyse particularspecimen cells and to immobilize the DNA structure to the sample supportmedium or substrate at discrete sample nodes 529. Additionally oralternatively, preservatives may be applied, embedded, impregnated, orotherwise incorporated onto or into the sample support medium; suchpreservatives may ensure the stability and fidelity of the DNA structurefor tens of years. Sample nodes 529, which may be characterized bydiscrete pellets or spheres as represented in FIGS. 5A and 5B, may beautomatically removed from a sample carrier and selectively deposited inparticular wells disposed in multi-well plates; samples deposited inparticular wells may, in turn, be selected for subsequent processing(e.g. such as with polymerase chain reaction (PCR) assays, and thelike).

Cross contamination is virtually eliminated by storing the samples ondiscrete sample nodes 529. In some instances, sample nodes 529 may beoptically separated from the sample carrier, thereby avoiding anymechanical contact involving a mechanical sample removal device duringretrieval, extraction, purification, packaging, and shipping. Moreover,since a sample carrier such as illustrated in FIGS. 4A–4C may beamenable to manipulation by standard robotics, an entire archivefacility may be easily automated to achieve high I/O rates (for example,greater than one hundred samples per day).

DNA which is archived and retrieved as set forth above with reference toFIGS. 3–5B may be well suited for large-scale genetic analysis, and mayyield samples which are superior (relative to conventional liquid phaseor cryogenic technologies) for pharmacogenetics or other types ofgenetic discovery analysis. Specifically, implementation of discretesample nodes 529 may automatically standardize the quantity and qualityof DNA storage due to the inherent loading properties of the samplesupport medium and any embedded chemicals serving to diminish PCRinhibitors; accordingly, the requirements and complexities ofquantification procedures following purification in conventional DNAextraction may be simplified, reduced, or eliminated entirely.Additionally, desiccated archive samples are not continuously degradedduring repeated freezing and thawing cycles as is common in cryogenicsystems.

FIG. 5C is a simplified block diagram illustrating one embodiment of asystem and method of removing a sample node from a sample carrierstructural array. As indicated, a removed sample node 529 may bedeposited in a sample container such as a well 531 in a standard ormodified multi-well plate (FIGS. 4A–4C); the remainder of the samplecarrier to which structural array 520C is attached and the remainder ofthe multi-well plate have been omitted from FIG. 5C for clarity.

Structural array 520C may be supported from a sample carrier by a samplesite positioning member 513 and a sample site member 514. As set forthin detail above, a discrete sample node 529 may be attached to samplestructure 524 at attachment point 525. In the FIG. 5C embodiment, alaser 599 may provide sufficient energy in the form of coherent light toattachment point 525 to remove sample node 529. Those of skill in theart will appreciate that other means, mechanisms, or devices may beemployed to remove sample node 529 from structural array 520C;accordingly, a cutting or clipping apparatus, micro-electromechanicaldevices (MEMS), or electrical circuit elements such as fuses, forexample, may be employed in lieu of laser 599 to provide energynecessary to separate sample node 529 from sample structure 524.

As discrete sample nodes 529 are removed from structural array 520Cduring the useful life of a given sample carrier, fewer samplestructures 522,524 may be supporting a sample node 529, i.e. fewersample nodes 529 remain. Accordingly, the laser in the exemplary FIG. 5Cembodiment may be enabled to identify or otherwise to ascertain thelocation of a particular sample node 529 targeted for removal. In thatregard, each sample structure 522,524 and its respective attachmentpoint 523,525 may be addressed and catalogued, for example.

Addressing or location information may be stored in a data storagemedium as described above with reference to FIG. 3, and may enable laser599 or other sample node removal means to identify and to target aspecific attachment point 523,525 supporting a discrete sample node 529on structural array 520C. Where the particular structural arrangement orconfiguration of structural array 520C is known and sample nodeaddressing information is stored as one or more data records,computerized robotic systems or computer-targeted laser 599 may becontrolled precisely to remove a selected sample node 529; similarly,the system may be apprised, through updated data records, of samplenodes which have been removed such that a detailed search of the entirestructural array 520C may not be required for subsequent sample noderemoval operations.

Additionally or alternatively, laser 599 or another sample removaldevice, such as a robotic clipping mechanism, for example, may beequipped with machine vision or other optical sensors. In thisembodiment, a sample locator device may gather optical information whichmay subsequently be used to guide a sample node removal apparatus suchas laser 599 in an interactive manner, ie. the system may methodicallyexamine each sample structure 522,524 in a predetermined order, forexample, or under control of an operator, until a sample structure522,524 supporting a sample node 529 is detected. This embodiment may beimplemented in situations where the configuration or orientation of allthe components of structural array 520C is not known or has changed(e.g. due to breakage or structural failure), or where the history ofsample node removal operations for a given structural array 520C is notknown; in such situations, a detailed “map” or other indication ofremaining sample node locations may not be available.

FIG. 5D is a simplified block diagram illustrating another embodiment ofa system and method of removing a sample node from a sample carrierstructural array. As in the FIG. 5C embodiment, a removed sample node529 may be deposited in a sample container 531 such as a well in astandard or modified multi-well plate, a test tube, or other vessel. Theomission of a sample structure positioning member from FIG. 5D isrepresentative of the fact that a given sample carrier may support onlya single structural array 520D.

In this embodiment, structural array 520D may be supported simply by asample site member 514, which may include an identification structure518 bearing a label or other identifying indicia 519 such as a bar code,serial number, and the like, substantially as described above.

A sample removal device 599 may be employed to remove sample node 529from structural array 520D; accordingly, sample removal device 599 maygenerally comprise an optical component 598, a positioning component597, and a clipping component 596.

Optical component 598 may generally comprise machine vision technology,video cameras, or other optical sensors which are capable of identifyingor locating the elements of structural array 520D using instruments orreceptors which are sensitive to various portions of the electromagneticspectrum. In this embodiment, optical information (from the visibleportion of the spectrum) or other electromagnetic information (such asmicrowave or infrared frequencies, for example) may be used to ascertainthe configuration and arrangement of structural array 520D. Theforegoing information may be used to automate the remaining componentsof sample removal device 599, for example; a completely automatedrobotic system may be developed around the functionality of opticalcomponent 598. Alternatively, output from optical component 598 may betransmitted or otherwise displayed in visual form for a system operator,who may control other elements of sample removal device 599 inaccordance with optical information regarding structural array 520Dobtained and provided by optical component 598.

Whether automated or operator-controlled, positioning component 597 maybe employed to guide clipping component 596 to an appropriate positionrelative to structural array 520D to remove a targeted sample node 529.In that regard, positioning component 597 may include some or all of thefollowing: servos; motors; hydraulic or electromechanical arms,appendages, or conveyors; gyroscopes; rotating shafts; pistons; gears;guide rails; support beams; and other elements generally known in theart for translating and articulating apparatus in three dimensions.

As set forth above, positioning component 597 may be operative to moveclipping component 596 or another sample node removal apparatus.Additionally or alternatively, positioning component 597 may beconstructed and operative to move structural array 520D or the samplecarrier to which it is attached. For example, structural array 520D orthe sample carrier may be mounted on a movable stage which translates inone or two dimensions. Whether positioning component 597 moves clippingcomponent 596, structural array 520D, or both, it will be appreciatedthat such a mechanical positioning system may bring a sample noderemoval device into a desired position relative to structural array520D, i.e. enabling removal of a targeted sample node 529.

As noted above with reference to FIG. 5C, various devices such aslasers, micro-electromechanical devices (MEMS), or electrical circuitelements may be employed to remove a targeted sample node 529 from astructural array. The exemplary FIG. 5D embodiment of clipping component596 comprises a mechanical clipper 595 which may be operative to seversample structure 524 at attachment point 525. It will be appreciatedthat use of a mechanical device such as clipper 595 may require physicalcontact with sample structure 524 during normal operation; to avoid riskof cross contamination from one sample removal operation to the next, itmay be desirable to ensure that sample structure 524 is free of specimenmaterial or other possible contaminants at the point at which clipper595 makes contact.

FIG. 5E is a simplified block diagram illustrating one embodiment of asample node identification or location system. To maximize the densityof samples maintained in an archive facility such as illustrated inFIGS. 1–3, biomolecules (such as DNA and proteins, for example) ornon-biological samples to be archived may be tagged electronically forsubsequent identification. Recently, micro-transceiver systems have beendeveloped by researchers and proposed for use in active drug deliverytechniques. As illustrated in FIG. 5E, for example, an electronicmicro-transceiver 590A, may be integrated into a discrete sample node529; additionally or alternatively, a transceiver 590B may be attachedto, or integrated into, sample structure 524 proximal to attachmentpoint 525.

As set forth above, biomolecules or other sample material may beattached on the surface (or may penetrate into the sample supportmedium) of sample node 529 for high density archiving. Amicro-transceiver 590A,590B may transmit omni-directional RF signals,for example, enabling a receiver at a robotic system to identify and tolocate sample node 529 using associated signature signal frequencies,transmission patterns, or other information. In this embodiment, aunique signal transmitted by transceiver 590A,590B may be received bythe positioning component 597 in FIG. 5D and used to direct thepositioning of robotic instrumentation or sample removal component 596.

Additionally or alternatively, a remote control system maintained at anarchive facility may transmit signals to transceivers 590A and 590B toinitiate operation of MEMS, for example, or to activate microcircuits orcircuit elements operative to remove sample node 529 from samplestructure 524. In the foregoing manner, sample node removal may betriggered electronically based upon signals transmitted to transceivers590A and 590B.

As described above, it may be desirable to ensure that sample structure524 is free of specimen material or other possible contaminants to avoidrisk of cross contamination. The FIG. 5E embodiment illustrates a region594 representing the point at which a mechanical clipping device maymake contact with sample structure 524. As set forth in more detailbelow, after specimen material is transferred to sample node 529, samplestructure 524 or the entire structural array or sample carrier, forinstance, may be washed or cleaned to remove contaminants or specimenresidue from region 594 or the entirety of sample structure 524.

FIG. 6 is a simplified flow diagram illustrating one embodiment of amethod of preparing an archive sample for analysis. An archive sample tobe analyzed may be identified or selected at block 601. For example, aresearcher may browse a list or catalogue of available samples (e.gmaintained at an archive facility as described above with reference toFIGS. 1–3); the list of archive samples may additionally becross-referenced with data records containing information related tosample sources as set forth in detail above, for example. In this sense,identifying or selecting the sample to be analyzed may simply representa process of designating or otherwise indicating a sample or type ofsample which may be appropriate for the intended analytical procedure.

Upon identification of a suitable sample or sample type, a samplecarrier which supports one or more appropriate sample nodes (i.e. asample node carrying the selected sample) may be identified and locatedas indicated at block 602. As with identification of a sample at block601, locating a sample carrier at block 602 may be executed manually,for example, by a researcher or a technician; alternatively,identification of a sample and location of a sample carrier may beautomated, for example with bar code readers and robotic sample carrierretrieval apparatus, as described above with reference to FIGS. 3 and 5.

At blocks 603 and 604, a structural array and a sample node may beidentified and located as set forth above with reference to FIGS. 5C–5E.Accurate address or location information may be maintained in a datastorage medium such that location of a structural array and a particularsample node may be accomplished without the use of optical systems ormachine vision techniques. In some embodiments, however, it may bedesirable to identify and to locate a discrete sample node actively, forexample, with the assistance of optical sensors or video signalinformation.

Removal of one or more identified sample nodes at block 605 may requireimplementation of a sample node removal device or means for separatingthe sample node from its respective sample structure. As set forthabove, suitable devices or apparatus include, but are not limited to,the following: targeted lasers; automated or manually controlledclipping, cutting, slicing, or breaking tools; programmable MEMS, whichmay be small enough and sufficiently agile to maneuver on the componentsof the structural array illustrated in FIGS. 5A–5E; electrical fuseswhich, when blown, may create sufficient heat to destroy the attachmentpoint thereby to separate a sample node from its respective samplestructure; or any other mechanisms configured and operative to deliverenough energy to the sample structure to remove the sample node.

As described above, each structural array, and consequently its samplenodes, may be positioned and dimensioned in a predetermined spatialrelationship, particularly with respect to one or more samplecontainers. A sample node removed from a structural array (block 605),may be deposited in a sample container such as a well in a multi-wellplate, a test tube or other experimental or storage vessel, a paper orcardboard bindle, a shipping container, and the like.

As indicated at block 606, a removed sample node may be prepared foranalysis. The preparation indicated in the FIG. 6 embodiment mayrepresent any or all of the following, inter alia: addition of reagentsor other chemicals to a sample container; purification of the sampleremoved from the sample carrier; washing, packaging, and shipping orother transportation to a remote site for analysis; and so forth.

FIG. 7 is a simplified flow diagram illustrating one embodiment of asample archival method. As indicated at block 701, the storage orarchival process may generally begin with acquiring consent from apatient or other specimen source. Much like the conventional archivingprocess, informed consent may be obtained by a professional recruiterafter explaining the nature of the research to be conducted at anarchive facility and any techniques or technologies employed by thearchive facility to ensure specimen source confidentiality. It will beappreciated that, in the case of non-biological specimens, for example,acquiring informed consent at block 701 may be neither possible nornecessary.

Information concerning or relating to the specimen source may beobtained as indicated at block 702. By way of example, a questionnaireor other form may be completed by the specimen source (e.g. a patient ora patient's guardian or representative) with the aid of a trainedprofessional; the questionnaire or form may be electronic, promptingcomputer input responses. Additionally or alternatively, some or all ofthe information obtained from the specimen source may be oral or handwritten; in this exemplary embodiment, a technician or data entryprofessional may input relevant information into a computer forrecordation in a database. A standardized or modified computerspreadsheet or other proprietary application software which iscompatible with the database may be used for data recordation. In someembodiments, data transcription errors may be minimized and maximumefficiency may be achieved where source- and specimen-specificinformation is input directly into a computerized system.

As depicted at block 703, a unique code, serial number, or otheridentifier may be assigned to the information associated with thespecimen and its source. As illustrated and described in detail abovewith reference to the sample carriers of FIGS. 4A and 5D, a respectivebar code or other identifying indicia may be used to identify specificsamples. In the case of specimens and source-specific information, suchan identifier may be assigned early in the archival process, possiblyeven before the specimen is obtained, as in the FIG. 7 embodiment.Identification of a specimen source and accurate association andcross-referencing with, for instance, the medical history of the sourceor other relevant information, may facilitate efficiency and properinterpretation of results in large-scale DNA or genomic studies, forexample.

Data specific to the specimen and the source may be recorded as datarecords in a database as indicated at block 704. As is generally knownin the art, data records may be accessed or retrieved in accordance withthe unique identifier associated therewith and assigned as set forthabove. As illustrated and described in detail above with reference toFIG. 3, data storage media serving as central information repositoriesmay be maintained at various locations in an archive facility. Data maybe transmitted to an archive facility, for example, via a networkconnection such as described above; in that regard, a secure internetconnection employing Secure Sockets Layer (SSL) encryption technology(128-bit encryption) or a VPN connection (168 bit encryption) may ensuredata integrity and confidentiality of sensitive information. Informationassociated with each contributing specimen source and transmitted to thearchive facility may be formatted in accordance with databaserequirements, for example, and subsequently made available to archivefacility clients via the network connection; in some embodiments,database formats and access authorizations may be selected to preservespecimen source confidentiality.

A specimen may be obtained from the source and associated with thecorrect unique identifier as indicated at block 705. For example, bloodmay be drawn from a patient by a member of a pathology nursing staff. Aportion of a standard blood draw (e.g. approximately 1–5 ml of a total10 ml draw) may be used to create samples for use in conjunction with asample carrier as described in detail above with reference to FIGS. 4and 5.

In accordance with this embodiment, a sample carrier may generallysupport one or more structural arrays, each comprising a plurality ofdiscrete sample nodes. As set forth above, each sample node may beoperative to carry a sample on a sample support medium. Some of theblood drawn may be deposited in a specimen container, for example, atest tube or one or more wells in a multi-well plate. The structuralarrays of the sample carrier may selectively be placed in proximity tothe respective specimen containers such that the plurality of samplenodes are selectively exposed to respective specimens. The samplesupport medium at the sample nodes may absorb, lyse, or otherwise bindthe blood spotted in the respective specimen containers. In theforegoing exemplary manner, specimen material may be transferred todiscrete sample nodes as represented at block 706. In some embodiments,preservatives may be applied or the sample nodes may be allowed to drysuch that each sample is maintained in desiccated form.

Sample nodes or entire sample carriers may be washed or rinsed, forexample with detergents or other chemicals, to remove specimen residueor other contaminants from sample structures as described above. Thecleaning process, represented at block 707, may reduce the risk of crosscontamination potentially introduced by operation of the sample removaldevice.

As noted above with reference to FIGS. 4A and 5D, sample carriers may bebar-coded, labeled, tagged, or otherwise provided with uniqueidentifying indicia, decipherable by an optical scanner or machinevision technology, which may facilitate automated or manual sample andsample carrier tracking. A bar code or other identification on aparticular sample carrier may provide information related to the sourceof the specimen used for each structural array on the sample carrier;further, the identifying indicia may also provide information related tothe structural arrangement or configuration of each structural array,i.e. the number of discrete sample nodes in a particular structuralarray, information concerning the spatial orientation of each discretesample node, and so forth. The location of each sample within the samplecarrier may be recorded as indicated at block 708; this recordation maybe coordinated with production of the bar code or other indicia for thesample carrier.

Covered storage carriers may be shipped to an archive facility fromremote locations, i.e. wherever specimens are obtained, typically byexpress mail. Since shipping blood or other biological samples in adesiccated or dry state does not require treatment as a hazardousmaterial, sample carriers supporting desiccated samples may beconveniently shipped anywhere in the world.

At an archive facility such as described above with reference to FIG. 3,robotics or automated mechanical systems may be used to place samplecarriers in receptacles (block 709). Receptacles may be embodied inshelves, drawers, racks, or other structures constructed to receivesample carriers; accordingly, the form and particular structuralconfiguration of receptacles at an archive facility may generally be afunction of the type and configuration of the sample carriers to bestored.

In one embodiment, an automated shelf or receptacle for storage andretrieval may be constructed to accommodate a sample carrier engagedwith a multi-well plate as described above with reference to FIG. 4A. Inthis embodiment, longitudinal frame elements of the sample carrier mayextend beyond the multi-well plate. A robotic gripping mechanism maygrasp the entire assembly (i.e. the sample carrier and the multi-wellplate), or only the sample carrier, depending upon the orientation ofthe gripping mechanism relative to the receptacle.

It will be appreciated that various alternatives exist with respect tothe FIG. 7 embodiment, and that the presented order of the individualblocks is not intended to imply a specific sequence of operations to theexclusion of other possibilities; the particular application and overallsystem requirements may dictate the most efficient or desirable sequenceof the operations set forth in FIG. 7. For example, specimen acquisitionand association with an identifier (represented at block 705) mayprecede block 704, or may even occur prior to obtaining source-specificinformation at block 702, provided that appropriate provisions are madefor assigning a unique identifier. Similarly, recordation of thelocation of samples at block 708 may precede, or occur simultaneouslywith, transfer of specimen material to discrete sample nodes at block706 in certain situations.

FIG. 8 is a simplified flow diagram illustrating one embodiment of amethod of retrieving and preparing an archive sample for analysis. Asindicated at block 801, the archive sample retrieval process in anexemplary embodiment may generally begin with receipt of a request. Amedical researcher or technician, for instance, may request retrieval ofblood or DNA samples. Such requests may be transmitted from remotenetwork clients across a communication network. In situations where aresearcher is interested in a specific disease or a specific type ofanalysis, the request may be related to, or include relevant informationwith respect to, a particular type of experiment or analysis, forexample.

In an embodiment such as depicted and described above with reference toFIGS. 1–3, for example, a researcher at a remote network client locationmay transmit a request to an archive facility via a network. Remoteinquiries may seek to ascertain the availability of samples which may beappropriate for the intended experimentation, and may include requestsfor access to data records or other clinical information related tosamples and sample sources; as noted above, such data records may bemaintained in one or more data structures at the archive facility.Through Boolean search queries, for example, or other data searchingtechniques which are generally known in the art, one or more suitablesamples may be identified responsive to the request; suitability ofparticular samples may be based upon relevant clinical data and history.Sample identification is generally depicted at block 802, and may befacilitated by random sample selection from designated or specifiedsample categories or sample types. Accordingly, broad categoriescontaining many samples, all of which satisfy selected criteria, may benarrowed automatically through random selection of particular sampleswithin the defined categories.

In some embodiments, a purchase order specifying some or all of theidentified samples may be submitted, followed by a request that thesamples be prepared for shipment to a remote location; additionally oralternatively, a researcher may request that certain analyses,experiments, or portions thereof be performed using the identifiedsamples at the archive facility. In any event, a sample carriersupporting the identified sample may be located in the archive facility(block 803). As described in detail above, location and retrieval ofparticular sample carriers may be facilitated by unique identifyingindicia disposed on each sample carrier in the archive facility;robotics and machine vision or bar code reader technology may enableautomatic location and retrieval of sample carriers. Alternatively, atechnician or administrator at the archive facility may locate andretrieve one or more sample carriers at block 803 manually.

As indicated at block 804, preparation of a sample for analysis mayinvolve detecting a location of a discrete sample node on the retrievedsample carrier; as set forth above with reference to the sample carriersillustrated in FIGS. 4 and 5, structural arrays and sample structuresmay support a plurality of discrete sample nodes in a predeterminedspatial relationship relative to each other and relative to a samplecontainer such as a test tube or a particular well of a multi-wellplate. As sample nodes are removed from a particular sample carrierduring its useful life, the efficient detection of sample structures towhich sample nodes are still attached may increase overall systemthroughput. As noted above, detecting the location of a sample node on asample carrier may be facilitated by, inter alia, data records relatedto previous sample removal operations, machine vision or opticaltechnology, or operator-assisted positioning tools for robotic sampleremoval mechanisms.

Following detection or location, discrete sample nodes may be removedfrom the sample carrier as indicated at block 805. Removal of samplenodes may be performed with optical equipment as illustrated in FIG. 5C;as described above, the FIG. 5C embodiment may virtually eliminate risksof cross contamination due to material transferred from one sample nodeto the next by a mechanical sample removal tool or device. Specifically,the FIG. 5C embodiment may employ a laser coupled to a precisepositioning system; lased, coherent light may sever the sample structuresupporting the sample node, depositing the sample node into a samplecontainer for future processing.

Alternatively, the mechanical clipper (FIG. 5D) or equivalent cuttingdevices may be employed for sample removal at block 805; in anembodiment utilizing a mechanical sample node removal tool, the tool maybe constructed and operative to make contact only with the samplestructure supporting the sample node to be removed. Accordingly, crosscontamination between samples may be avoided, since the sample noderemoval device does not make contact with any sample material.

At decision block 806, a determination may be made with respect toshipping the samples. Where a request for shipment has been made by theresearcher, for example, the sample container into which the sample nodehas been deposited may be sealed and packaged for shipment; as indicatedat block 807, samples may be purified with one or more appropriateprocedures prior to shipment such that, upon arrival at a remotelocation, the samples may be in condition for immediate experimentation(block 899). By way of specific example, a PCR amplification may precedeshipment; the DNA attached to the sample support medium at the samplenode may serve as the DNA template, and PCR reagents may then bedeposited directly into the sample container.

Where shipping has not been requested, or where analysis is requestedprior to shipment, processing may proceed in accordance with the requestas indicated at block 808. Various testing, experimentation, andanalysis may be conducted at the archive facility or at a remotefacility as set forth in detail above. Test results, data, or otherrelevant information may be recorded as indicated at block 809;additionally or alternatively, the acquired data may be transmitted,either responsive to a specific request or automatically, for example,to a researcher at a remote location via a network connection asdescribed above with reference to FIGS. 1–3.

Those of skill in the art will appreciate that the FIG. 8 embodiment isprovided by way of example only, and that various alternatives exist. Inan embodiment accommodating both processing at an archive facility aswell as shipment of samples to a remote site, for example, theoperations indicated at blocks 807 and 899 may follow recordation andtransmission of experimental results at block 809. As anotheralternative, the determination at decision block 806 may directly followreception of a request (block 801) or sample identification (block 802);it is possible in this embodiment, for example, that an entire samplecarrier may simply be shipped directly to a remote location withoutsample node detection, removal, or analysis.

In addition to sample archival and retrieval, myriad DNA analysisservices may be provided to remote clients in conjunction withaffiliated genomics companies. For example, researchers may be primarilyinterested in the genotypes of specific patient or sample classes asopposed to the samples themselves. In this situation, remote clients mayspecify not only specific samples or sample categories of interest, butalso particular genes or gene sequences of interest. An affiliatedcompany, for example, under contract with the archive facility, maydesign a custom DNA chip used to genotype the selected samples;accordingly, genotyping results may be transmitted electronically (via asecure or encrypted network connection, for example) to a remote client.Since the sample nodes may be delivered in standard microtiter plates asset forth above, samples may be delivered in suitable condition forimmediate amplification for subsequent desired experimentation oranalysis.

The embodiments described above are scalable; as numerous archivefacilities are employed and networked, a vast database of samples andinformation related to sample sources may be statistically mined toreveal DNA-directed therapeutics and, ultimately, cures for many geneticailments.

The present invention has been illustrated and described in detail withreference to particular embodiments by way of example only, and not byway of limitation. Those of skill in the art will appreciate thatvarious modifications to the disclosed embodiments are within the scopeand contemplation of the invention. Therefore, it is intended that theinvention be considered as limited only by the scope of the appendedclaims.

1. A method of preparing an archive sample for analysis; said methodcomprising: identifying a sample to be analyzed; responsive to saididentifying, ascertaining a location of said sample on a discrete samplenode supported by a sample carrier; said discrete sample node comprisinga sample support medium operative to carry a discrete sample indesiccated form; responsive to said ascertaining, removing said discretesample node from said sample carrier; and preparing said sample foranalysis, wherein said sample is biological, and wherein said sample isa polynucleotide.
 2. The method of claim 1 wherein said identifyingcomprises interrogating a data structure.
 3. The method of claim 1wherein said ascertaining comprises utilizing an optical sensor.
 4. Themethod of claim 1 wherein said ascertaining comprises reading a barcode.
 5. The method of claim 1 wherein said ascertaining comprisesidentifying a unique signal transmitted from a transceiver attached tosaid discrete sample node.
 6. The method of claim 5 wherein saidremoving comprises transmitting a control signal to said transceiver. 7.The method of claim 1 wherein said removing comprises utilizing a laser.8. The method of claim 1 wherein said removing comprises utilizing amechanical clipping tool.
 9. The method of claim 1 wherein saidpreparing comprises depositing said discrete sample node in a samplecontainer.
 10. The method of claim 1 wherein said preparing compriseswashing sample material attached to said discrete sample node.
 11. Themethod of claim 1 wherein said preparing comprises amplifying saidpolynucleotide.
 12. A method of preparing an archive sample foranalysis; said method comprising: receiving a request related to anexperiment; identifying a sample suitable for said experiment;responsive to said receiving and said identifying, locating a samplecarrier supporting said sample on a discrete sample node; said discretesample node comprising a sample support medium operative to carry adiscrete sample in desiccated form; detecting a location of saiddiscrete sample node on said sample carrier; removing said discretesample node from said sample carrier; and preparing said sample foranalysis, wherein said detecting comprises obtaining video signalsoutput from an optical sensor.
 13. The method of claim 12 wherein saidlocating comprises interrogating a database maintaining records relatedto said sample carrier.
 14. The method of claim 12 wherein said locatingcomprises utilizing an optical sensor.
 15. The method of claim 12wherein said locating comprises reading a bar code.
 16. The method ofclaim 12 wherein said removing comprises automatically operating asample node removal device responsive to said obtaining video signals.17. The method of claim 12 wherein said removing comprises manuallyoperating a sample node removal device.
 18. The method of claim 12wherein said removing comprises utilizing a laser.
 19. The method ofclaim 12 wherein said removing comprises utilizing a mechanical clippingtool.
 20. The method of claim 12 wherein said preparing comprisesdepositing said discrete sample node in a sample container.
 21. Themethod of claim 12 wherein said preparing comprises washing samplematerial attached to said discrete sample node.
 22. The method of claim12 wherein said sample is non-biological.
 23. The method of claim 12wherein said sample is biological.
 24. A method of preparing an archivesample for analysis; said method comprising: receiving a request relatedto an experiment; identifying a sample suitable for said experiment;responsive to said receiving and said identifying, locating a samplecarrier supporting said sample on a discrete sample node; said discretesample node comprising a sample support medium operative to carry adiscrete sample in desiccated form; detecting a location of saiddiscrete sample node on said sample carrier; removing said discretesample node from said sample carrier; and preparing said sample foranalysis, wherein said sample is biological, and wherein said sample isa polynucleotide.
 25. The method of claim 24 wherein said preparingcomprises amplifying said polynucleotide.
 26. A method of preparing anarchive sample for analysis; said method comprising: identifying asample to be analyzed; said sample maintained in desiccated form andcarried on a sample support medium associated with a discrete samplenode; responsive to said identifying, obtaining said sample; preparingsaid sample for analysis; and selectively repeating said identifying,said obtaining, and said preparing at a rate sufficient to prepare inexcess of 100 samples for analysis per day wherein said sample isbiological, and wherein said sample is a polynucleotide.
 27. The methodof claim 26 wherein said identifying comprises interrogating a database.28. The method of claim 26 wherein said identifying comprises utilizingan optical sensor.
 29. The method of claim 26 wherein said obtainingcomprises automatically operating a sample node removal device.
 30. Themethod of claim 29 wherein said obtaining comprises utilizing a laser.31. The method of claim 29 wherein said obtaining comprises utilizing amechanical clipping tool.
 32. The method of claim 26 wherein saidpreparing comprises depositing said sample in a sample container. 33.The method of claim 26 wherein said preparing comprises washing saidsample.
 34. The method of claim 26 wherein said preparing comprisesamplifying said polynucleotide.
 35. The method of claim 26 wherein saidselectively repeating occurs at a rate sufficient to prepare in excessof 200 samples for analysis per day.
 36. The method of claim 26 whereinsaid selectively repeating occurs at a rate sufficient to prepare inexcess of 500 samples for analysis per day.